Department of Cardiac Surgery, Heart Center, University Hospital Leipzig, Leipzig, Germany.
Clin Exp Immunol. 2014 Apr;176(1):120-8. doi: 10.1111/cei.12254.
Extracorporeal photopheresis (ECP) has been used as a prophylactic and therapeutic option to avoid and treat rejection after heart transplantation (HTx). Tolerance-inducing effects of ECP such as up-regulation of regulatory T cells (T(regs)) are known, but specific effects of ECP on regulatory T cell (T(reg)) subsets and dendritic cells (DCs) are lacking. We analysed different subsets of T(regs) and DCs as well as the immune balance status during ECP treatment after HTx. Blood samples were collected from HTx patients treated with ECP for prophylaxis (n = 9) or from patients with histologically proven acute cellular rejection (ACR) of grade ≥ 1B (n = 9), as well as from control HTx patients without ECP (HTxC; n = 7). Subsets of T(regs) and DCs as well as different cytokine levels were analysed. Almost 80% of the HTx patients showed an effect to ECP treatment with an increase of T(regs) and plasmacytoid DCs (pDCs). The percentage of pDCs before ECP treatment was significantly higher in patients with no ECP effect (26·3% ± 5·6%) compared to patients who showed an effect to ECP (9·8% ± 10·2%; P = 0·011). Analysis of functional subsets of CD4⁺CD25(high)CD127(low) T(regs) showed that CD62L-, CD120b- and CD147-positive T(regs) did not differ between the groups. CD39-positive T(regs) increased during ECP treatment compared to HTxC. ECP-treated patients showed higher levels for T helper type 1 (Th1), Th2 and Th17 cytokines. Cytokine levels were higher in HTx patients with rejection before ECP treatment compared to patients with prophylactic ECP treatment. We recommend a monitoring strategy that includes the quantification and analysis of T(regs), pDCs and the immune balance status before and up to 12 months after starting ECP.
体外光分离术（ECP）已被用作预防和治疗心脏移植（HTx）后排斥反应的一种选择。已知 ECP 具有诱导耐受的作用，例如调节性 T 细胞（Tregs）的上调，但 ECP 对调节性 T 细胞（Treg）亚群和树突状细胞（DC）的具体作用尚不清楚。我们分析了 HTx 后 ECP 治疗期间不同 Treg 亚群和 DC 以及免疫平衡状态。从接受 ECP 预防治疗的 HTx 患者（n=9）或组织学证实的 1B 级以上急性细胞性排斥反应（ACR）患者（n=9）以及未接受 ECP 的 HTx 对照患者（HTxC；n=7）中采集血液样本。分析了 Treg 和 DC 亚群以及不同细胞因子水平。近 80%的 HTx 患者对 ECP 治疗有反应，Treg 和浆细胞样树突状细胞（pDC）增加。与对 ECP 有反应的患者（9.8%±10.2%）相比，无 ECP 作用的患者（26.3%±5.6%）在 ECP 治疗前 pDC 百分比明显更高（P=0.011）。对 CD4+CD25（高）CD127（低）Treg 的功能亚群分析显示，各组间 CD62L-、CD120b-和 CD147-阳性 Treg 无差异。与 HTxC 相比，ECP 治疗期间 CD39-阳性 Treg 增加。接受 ECP 治疗的患者 Th1、Th2 和 Th17 细胞因子水平升高。在开始 ECP 治疗之前，与接受预防性 ECP 治疗的患者相比，接受 ECP 治疗的 HTx 患者的排斥反应中细胞因子水平更高。我们建议在开始 ECP 之前和之后 12 个月内进行监测策略，包括 Treg、pDC 和免疫平衡状态的定量和分析。
